Search

Abstract Background Continuous loss of muscle mass and strength are the consequences of the ageing process, which increase the risk of falls among older people. Falls can lead to severe consequences such as bone fractures and hampered physical and psychological well-being. Regular exercise is the key to reversing muscle atrophy and relieving sarcopenia. However, the frailty of older people and the recent COVID-19 pandemic may affect their confidence to leave home to attend classes in the community. A feasible and effective alternative should be explored. Methods The primary objective is to evaluate the effectiveness of tele-exercise (TE) in relation to physical functioning and exercise adherence among community-dwelling older people at risk of falls in comparison with a community-based group (CB). The secondary objective includes evaluating older people’s experience with tele-exercise, emphasizing their psychological welfare, social well-being, and acceptance of the telehealth approach. The design, conduct, and report follow the SPIRIT guidelines (Standard Protocol Items: recommended items to address in a Clinical Trial Protocol and Related Documents). Older people will be recruited from 10 local community centres in Hong Kong and randomly allocated into two groups. All participants will attend the exercise training 3 days per week for 3 months but the mode of delivery will differ, either online as the tele-exercise group (TE) or face-to-face as the community-based group (CB). The outcome measures include muscle strength, physical function, exercise adherence and dropout rate, psychological and social well-being will be assessed at the baseline, and the 3rd, 6th and 12th month. Some participants will be invited to attend focus group interviews to evaluate their overall experience of the tele-exercise training. Discussion Tele-exercise reduces the barriers to exercise, such as time constraints, inaccessibility to facilities, and the fear of frail older people leaving their homes. Promoting an online home-based exercise programme for older people can encourage them to engage in regular physical activity and increase their exercise adherence even when remaining at home. The use of telehealth can potentially result in savings in cost and time. The final findings will provide insights on delivering exercise via telehealth to older people and propose an exercise delivery and maintenance model for future practice. Trial registration Chinese Clinical Trial Registry ( https://www.chictr.org.cn/hvshowprojectEN.html?id=219002&v=1.1 ), registration number: ChiCTR2200063370. Registered on 5 September 2022.

Abstract Quantifying neural activity in natural conditions (i.e. conditions comparable to the standard clinical patient experience) during the administration of psychedelics may further our scientific understanding of the effects and mechanisms of action. This data may facilitate the discovery of novel biomarkers enabling more personalized treatments and improved patient outcomes. In this single-blind, placebo-controlled study with a non-randomized design, we use time-domain functional near-infrared spectroscopy (TD-fNIRS) to measure acute brain dynamics after intramuscular subanesthetic ketamine (0.75 mg/kg) and placebo (saline) administration in healthy participants (n = 15, 8 females, 7 males, age 32.4 ± 7.5 years) in a clinical setting. We found that the ketamine administration caused an altered state of consciousness and changes in systemic physiology (e.g. increase in pulse rate and electrodermal activity). Furthermore, ketamine led to a brain-wide reduction in the fractional amplitude of low frequency fluctuations, and a decrease in the global brain connectivity of the prefrontal region. Lastly, we provide preliminary evidence that a combination of neural and physiological metrics may serve as predictors of subjective mystical experiences and reductions in depressive symptomatology. Overall, our study demonstrated the successful application of fNIRS neuroimaging to study the physiological effects of the psychoactive substance ketamine in humans, and can be regarded as an important step toward larger scale clinical fNIRS studies that can quantify the impact of psychedelics on the brain in standard clinical settings.

Abstract Background Weight gain is commonly observed during and after breast cancer treatment and is associated with poorer survival outcomes, notably in women with oestrogen-receptor positive disease. The aim of this qualitative study was to investigate the experiences and perceptions of oestrogen-receptor positive (ER +) female breast cancer patients (BCPs) regarding weight management behaviours during and after treatment. Secondly, to gain insight into the experiences of healthcare professionals (HCPs) regarding the provision of weight management advice to patients undergoing treatment. Methods Four focus groups involving 16 BCPs having a median (range) age of 51 (35–70 y) and three focus groups involving 21 HCPs aged 46 (29–62) were held at a university campus, local cancer support centre or clinical site. Data were analysed using Framework analysis. Results Four overarching themes (and 10 subthemes) were identified: (1) Treatment; (2) Support for lifestyle behaviour change; (3) Information availability for BCPs; (4) Knowledge of current evidence amongst HCPs. The physical and psychological consequences of treatment influenced motivation for weight management amongst BCPs. Social support for health promoting behaviours was viewed as important but was conflicting, requiring context-specific considerations. BCPs said they would have welcomed access to credible information (guided by HCPs) about the potential detrimental health effects of excess body weight and weight gain, together with advice on weight management via healthy eating and physical activity. HCPs felt that they had insufficient knowledge of public health dietary and physical activity recommendations or evidence-based interventions to confidently offer such advice. HCPs expressed concern that raising weight management issues would exacerbate distress or invoke feelings of guilt amongst BCPs, and cited time pressures on patient consultations as additional barriers to providing weight management support. Conclusion The study yielded novel insights into factors influencing weight management behaviours amongst overweight ER + BCPs. The results suggest that evidence-based information and support, which addresses key physical and psychological challenges to physical activity and dietary behaviours, offers the best route to sustainable weight management in this population.

Abstract Background Urethral duplication (UD) is reportedly rare. It is rarer in females. Knowledge on this anomaly comes from isolated report of cases. The aim of this review is to summarize information available on this anomaly thereby revealing gaps in knowledge, and to appropriately situate a recently managed case. Methods Publications on UD in English language from 2001 to 2021 were searched for in the literature. Of importance were age at presentation, class of UD, nature of associated penile deformity and other structural anomalies. Available information was used to synthesize opinions after descriptive analyses using SPSS® version 21 (IBM Co., Armonk, NY, USA). In addition, a recently managed case of UD was reported and appropriately situated in the discourse. Result In all, 115 articles met the inclusion criteria. Majority (75.7%) were individual case reports, while the rest were retrospective review of case series. These provided a total of 269 reported cases. Of this lot, 38 cases were excluded because they either had no Effmann’s class or were not described well enough for an Effmann’s class to be assigned. Ultimately, 231 cases formed the basis for this review. Male to female ratio was 12:1. Types III and IIB had more females. Types IIA 2 (26.0%), IIA 2 “Y” (26.4%) and IA (22.5%) were frequently reported. About 61.8% males and 68.4% females had no associated defects. Isolated dorsal chordee was prevalent (7.1%), especially among type IA (16.7%) UD. Reported in 10.4%, vesicoureteric reflux may not be attributable always to high pressure voiding. A boy who presented at the age of 18 years with Effmann type IA UD and an associated complex chordee of the penile shaft was reported. The complex nature of the chordee adds to the challenge of explaining associated penile defects in UD. Conclusion UD is rare, but reported from all parts of the globe. There are a number of associated defects involving the external genitalia and other organs reported in UD in the male. The mechanisms of these defects are yet to be fully understood.

ABSTRACT: The demand for chicken meat and eggs exceeds what can be produced in Tanzania, largely due to low productivity of the sector. Feed quantity and quality are the major factors determining the potential production and productivity of chickens. The present study explored the yield gap in chicken production in Tanzania and analyses the potential of increased chicken production as a result of closing the feed gaps. The study focused on feed aspects limiting dual-purpose chicken production in semi-intensive and intensive systems. A total of 101 farmers were interviewed using a semistructured questionnaire and the amount of feed provided to chickens per day was quantified. Feed was sampled for laboratory analysis and physical assessments were made of weights of chicken bodies and eggs. The results were compared with the recommendations for improved dual-purpose crossbred chickens, exotic layers, and broilers. The results show that the feeds were offered in insufficient quantity compared with the recommendations for laying hens (125 g/chicken unit/d). Indigenous chickens were fed 111 and 67 while the improved crossbred chickens were fed 118 and 119 g/chicken unit/d under semi-intensive and intensive systems, respectively. Most feeds fed to dual-purpose chickens were of low nutritional quality, particularly lacking in crude protein and essential amino acids in both rearing systems and breeds. Maize bran, sunflower seedcake, and fishmeal were the main sources of energy and protein in the study area. The study findings show that the important feed ingredients: protein sources, essential amino acids, and premixes were expensive, and were not included in formulating compound feeds by most chicken farmers. Of all 101 respondents interviewed, only one was aware of aflatoxin contamination and its effects on animal and human health. All feed samples contained a detectable concentration of aflatoxins and 16% of them exceeded the allowed toxicity thresholds (>20 µg/kg). We highlight the need for a stronger focus on feeding strategies and ensuring the availability of suitable and safe feed formulations.

Zoos strive to create experiences that inspire positive feelings toward animals which lead to conservation behaviors in their visitors. However, concerns regarding the welfare of animals living in zoos present a challenge in creating positive zoo experiences and promoting the conservation agenda and moral authority of these cultural institutions. This research explores connections between zoo visitors’ positive affective responses and their assessments of animal welfare before and after two giraffes were introduced to a group of four giraffes in a multi-species savannah exhibit. A self administered questionnaire was completed by 499 visitors to the Conservation Society of California’s Oakland Zoo. The questionnaire measured visitors’ predispositions, affective responses, and assessments of animal welfare. Results suggest that visitors’ assessments of animal welfare, positive affective experience, and predisposition are positively correlated. Further, visitor assessments of animal welfare are generally more positive after the addition of new giraffes. Although visitors tended to report that the giraffes were very healthy and well cared for, they responded less positively when asked about how happy the giraffes were and how adequately sized their exhibit was. The findings suggest that understanding and improving zoo visitors’ assessments of animal welfare is important in improving positive experiences and conservation education outcomes during a visit to the zoo.

ABSTRACT: The poultry industry in Tanzania has grown steadily over the past decade. We surveyed 121 chicken farming households along an intensification gradient from backyard to semi-intensive and intensive production systems based on rearing system and assumed purpose and poultry breed in the Iringa region. About 30% of households had more than one breed and/or rearing system combination. The subdivision of poultry systems was refined by adding the size of the flocks to highlight variation in scale of operations. On this basis we distinguished 3 main types: 1) subsistence small-scale free-range chicken production; 2) market-oriented small to medium scale semi-intensive and 3) small to medium-large scale intensive systems. ‘Intensification’ involves the transition from keeping indigenous chickens to improved dual-purpose and exotic breeds driven by greater productivity and potential for income generation. The more intensive the production system, the more the intensity and diversity of diseases identified by farmers as their main problem, which was partly attributed to the greater sensitivity of the improved breeds, poor veterinary measures, and the high chicken density facilitating disease spread. Based on the survey we constructed a problem tree to classify the underlying constraints and their interrelations, and to identify common root causes, based on which we propose practical solutions to improve chicken production. Development of medium-large scale systems is particularly constrained by a limited supply of 1-day-old chicks and theft. By contrast, intensification of small-scale systems is constrained by limited access to quality feed, vaccines and medicines, capital, and lack of a reliable market, partly due to the absence of farmer organization. These constraints can be addressed through formation of producer groups and promotion of outgrower and enterprise development models. Enterprise development appears to be the most promising business model for smallholder chicken farmers given that it allows farmers more freedom in decision-making and management while strengthening linkages with input suppliers and output markets to ensure a viable and profitable business.

Abstract Large carnivores play critical roles in terrestrial ecosystems but have suffered dramatic range contractions over the past two centuries. Developing an accurate understanding of large carnivore diets is an important first step towards an improved understanding of their ecological roles and addressing the conservation challenges faced by these species. The puma is one of seven large felid species in the world and the only one native to the non‐tropical regions of the New World. We conducted a meta‐analysis of puma diets across the species’ range in the Americas and assessed the impact of varying environmental conditions, niche roles, and human activity on puma diets. Pumas displayed remarkable dietary flexibility, consuming at least 232 different prey species, including one Critically Endangered and five Endangered species. Our meta‐analysis found clear patterns in puma diets with changing habitat and environmental conditions. Pumas consumed more larger‐bodied prey species with increasing distance from the equator, but consumption of medium‐sized species showed the opposite trend. Puma diets varied with their realized niche; however, contrary to our expectations, puma consumption of large species did not change with their trophic position, and pumas consumed more small prey and birds as apex predators. Consumption of domestic species was negatively correlated with consumption of medium‐sized wild species, a finding which underscores the importance of maintaining intact native prey assemblages. The tremendous dietary flexibility displayed by pumas represents both an opportunity and a challenge for understanding the puma’s role in ecosystems and for the species’ management and conservation. Future studies should explore the linkages between availability and selection of primary and other wild prey, and consequent impacts on predation of domestic species, in order to guide conservation actions and reduce conflict between pumas and people.

This paper presents a complete procedure on prototyping using the FPGA of the STEMlab board and is intended to serve as a guide for developers, students and researchers interested in speeding up their projects and experiments. Due to the reconfigurability of its internal circuitry, being as simple as a code modification (using hardware description language), FPGA technology allows testing of several controller topologies and/or parameters without the need of any physical change at hardware. This feature allows a much faster development cycle of either commercial products or academic experiments. Besides the reconfigurability of the FPGA, the STEMlab board also offers the advantage of several peripheral already available, which includes, among others, high speed analog-to-digital and digital-to-analog converters, Ethernet communication and a dual-core ARM processor capable of running a Linux operating system. In this paper, a didactic method of use of this board is presented, from getting started to a complete academic and industrial application: detection of early damage on an induction motor using frequency response analysis.

This paper presents the detailed project of a modular educational kit to be used in research and teaching activities in the area of power electronics - with emphasis on applications in medium voltage multilevel converters. The half bridge topology has been chosen for the submodules, as they can be arranged together in a multitude of other topologies. A system composed by a mother board and daughter cards is presented. A DSP control card and a FPGA System-On-Module are inserted in the mother board in order to control the half bridge submodules. The targets of this project are applications in medium voltage - hence, the communication between the submodules and the FPGA/DSP is performed through optical fibers. Also a self power system is presented for the submodules, in order for them to operate at floating potentials. Experimental results have been presented for the most usual topologies of converters, including a Modular Multilevel Converter operating at 2000V.

Soft materials are usually defined as materials made of mesoscopic entities, often self-organised, sensitive to thermal fluctuations and to weak perturbations. Archetypal examples are colloids, polymers, amphiphiles, liquid crystals, foams. The importance of soft materials in everyday commodity products, as well as in technological applications, is enormous, and controlling or improving their properties is the focus of many efforts. From a fundamental perspective, the possibility of manipulating soft material properties, by tuning interactions between constituents and by applying external perturbations, gives rise to an almost unlimited variety in physical properties. Together with the relative ease to observe and characterise them, this renders soft matter systems powerful model systems to investigate statistical physics phenomena, many of them relevant as well to hard condensed matter systems. Understanding the emerging properties from mesoscale constituents still poses enormous challenges, which have stimulated a wealth of new experimental approaches, including the synthesis of new systems with, e.g. tailored self-assembling properties, or novel experimental techniques in imaging, scattering or rheology. Theoretical and numerical methods, and coarse-grained models, have become central to predict physical properties of soft materials, while computational approaches that also use machine learning tools are playing a progressively major role in many investigations. This Roadmap intends to give a broad overview of recent and possible future activities in the field of soft materials, with experts covering various developments and challenges in material synthesis and characterisation, instrumental, simulation and theoretical methods as well as general concepts.

ObjectivePrevalence of type 2 diabetes (T2D) is disproportionately higher in younger outwardly lean Asian Chinese compared to matched Caucasians. Susceptibility to T2D is hypothesised due to dysfunctional adipose tissue expansion resulting in adverse abdominal visceral and organ fat accumulation. Impact on early risk, particularly in individuals characterised by the thin-on-the-outside-fat-on-the-inside (TOFI) phenotype, is undetermined.MethodsSixty-eight women [34 Chinese, 34 Caucasian; 18–70 years; body mass index (BMI), 20–45 kg/m2] from the TOFI_Asia study underwent magnetic resonance imaging and spectroscopy to quantify visceral, pancreas, and liver fat. Total body fat was (TBF) assessed by dual-energy x-ray absorptiometry, and fasting blood biomarkers were measured. Ethnic comparisons, conducted using two-sample tests and multivariate regressions adjusted for age, % TBF and ethnicity, identified relationships between abdominal ectopic fat depots with fasting plasma glucose (FPG), insulin resistance (HOMA2-IR), and related metabolic clinical risk markers in all, and within ethnic groups.ResultsDespite being younger and of lower bodyweight, Chinese women in the cohort had similar BMI and % TBF compared to their Caucasian counterparts. Protective high-density lipoprotein cholesterol, total- and high-molecular weight adiponectin were significantly lower, while glucoregulatory glucagon-like peptide-1 and glucagon significantly higher, in Chinese. There were no ethnic differences between % pancreas fat and % liver fat. However, at low BMI, % pancreas and % liver fat were ∼1 and ∼2% higher in Chinese compared to Caucasian women. In all women, % pancreas and visceral adipose tissue had the strongest correlation with FPG, independent of age and % TBF. Percentage (%) pancreas fat and age positively contributed to variance in FPG, whereas % TBF, amylin and C-peptide contributed to IR which was 0.3 units higher in Chinese.ConclusionPancreas fat accumulation may be an early adverse event, in TOFI individuals, with peptides highlighting pancreatic dysfunction as drivers of T2D susceptibility. Follow-up is warranted to explore causality.

The World Health Organization (WHO) was informed on December 2019 about a coronavirus pneumonia outbreak in Wuhan, Hubei province (China). Subsequently, on March 12, 2020, 125,048 cases and 4,614 deaths were reported. Coronavirus is an enveloped RNA virus, from the genus Betacoronavirus, that is distributed in birds, humans, and other mammals. WHO has named the novel coronavirus disease as COVID-19. More than 80 clinical trials have been launched to test coronavirus treatment, including some drug repurposing or repositioning for COVID-19. Hence, we performed a search in March 2020 of the clinicaltrials.gov database. The eligibility criteria for the retrieved studies were: contain a clinicaltrials.gov base identifier number; describe the number of participants and the period for the study; describe the participants’ clinical conditions; and utilize interventions with medicines already studied or approved for any other disease in patients infected with the novel coronavirus SARS-CoV-2 (2019-nCoV). It is essential to emphasize that this article only captured trials listed in the clinicaltrials.gov database. We identified 24 clinical trials, involving more than 20 medicines, such as human immunoglobulin, interferons, chloroquine, hydroxychloroquine, arbidol, remdesivir, favipiravir, lopinavir, ritonavir, oseltamivir, methylprednisolone, bevacizumab, and traditional Chinese medicines (TCM). Although drug repurposing has some limitations, repositioning clinical trials may represent an attractive strategy because they facilitate the discovery of new classes of medicines; they have lower costs and take less time to reach the market; and there are existing pharmaceutical supply chains for formulation and distribution.

Objective. To identify studies on the competence of Culex mosquitoes as vectors for the transmission of Zika virus (ZIKV) around the globe. Methods. We performed an integrative review to identify relevant articles on specific experiments to determine whether Culex mosquitoes are vectors for ZIKV. The sources we used for our research were the Brazilian Periódicos CAPES electronic portal (MEDLINE/PubMed, ScienceDirect Journals, Nature Publishing Group, SciELO, Springer Link, and 250 other databases) and gray literature. Results. We identified 344 studies, of which 36 were considered for this review. In 8 studies, infection in salivary glands of Culex quinquefasciatus, Culex restuans, Culex tarsalis, and Culex coronator was detected. Cx. quinquefasciatus was the most studied among those confirmed as potential ZIKV vectors, and only strains of Asian lineages (THA/2014/SV0127-14; SZ01 (2016)) and American lineages (BRPE243 (2015); PRVABC59 (2015)) can infect the salivary glands of Culex mosquitoes. The tested African strains (MR766 and DAK AR 41525) were unable to infect salivary glands. Conclusions. There is still a lack of compelling evidence that indicates Culex spp. are a competent ZIKV vector, but they should remain a target for further monitoring studies, especially regarding ZIKV transmission to other species. Furthermore, studies should not be limited to studying whether their salivary glands are infected.

This paper presents the development and operation on 13.8kV distribution systems of a peak-shaving equipment with battery energy storage. This equipment injects active power to grid during peak times (when the cost of energy is higher) and charges its battery banks from the grid at the off-peak times (when the energy has a low producing cost). The equipment is based on a multilevel converter coupled to the grid through a 2.4kV:13.8kV transformer. In addition to the peak-shaving functionality, a feature of compensation of harmonics on the distribution voltage is included, without the need for any extra sensor nor hardware (apart from the ones already in use for the peak-shaving). The compensation of voltage harmonics is performed through the emulation of a harmonic resistance in order to damp resonances between system impedances that are excited by non-linear loads. This approach is very appealing to distribution systems, where the non-linear loads are not accessible and are scattered. Experimental results obtained on a 13.8kV test substation are presented.

Abstract Mice have been increasingly used as preclinical model to elucidate mechanisms and test therapeutics for treating intervertebral disc degeneration (IDD). Several intervertebral disc (IVD) histological scoring systems have been proposed, but none exists that reliably quantitate mouse disc pathologies. Here, we report a new robust quantitative mouse IVD histopathological scoring system developed by building consensus from the spine community analyses of previous scoring systems and features noted on different mouse models of IDD. The new scoring system analyzes 14 key histopathological features from nucleus pulposus (NP), annulus fibrosus (AF), endplate (EP), and AF/NP/EP interface regions. Each feature is categorized and scored; hence, the weight for quantifying the disc histopathology is equally distributed and not driven by only a few features. We tested the new histopathological scoring criteria using images of lumbar and coccygeal discs from different IDD models of both sexes, including genetic, needle‐punctured, static compressive models, and natural aging mice spanning neonatal to old age stages. Moreover, disc sections from common histological preparation techniques and stains including H&E, SafraninO/Fast green, and FAST were analyzed to enable better cross‐study comparisons. Fleiss's multi‐rater agreement test shows significant agreement by both experienced and novice multiple raters for all 14 features on several mouse models and sections prepared using various histological techniques. The sensitivity and specificity of the new scoring system was validated using artificial intelligence and supervised and unsupervised machine learning algorithms, including artificial neural networks, k‐means clustering, and principal component analysis. Finally, we applied the new scoring system on established disc degeneration models and demonstrated high sensitivity and specificity of histopathological scoring changes. Overall, the new histopathological scoring system offers the ability to quantify histological changes in mouse models of disc degeneration and regeneration with high sensitivity and specificity.

Understanding the transport of nanomaterials, especially nanoparticles, through a porous medium has major implications in many different fields. Here the authors report the ability of soft nanoparticles to shrink in confined environments, therefore boosting their diffusion compared to hard, non-deformable particles.

It has been predicted theoretically that the density of self-propelled particles whose speed is spatially dependent should be inversely proportional to the local speed. Here the authors present a systematic check of this prediction in a system of light-activated E. coli.

BackgroundThe use of face masks by children for the prevention of COVID 19 is still controversial, especially with regards to who should wear the face mask and at what age.ObjectivesThe study aimed to ascertain the perception of mothers on masking in children as a preventive strategy for COVID-19.MethodologyThis was a cross-sectional study carried out in two health institutions among 387 mothers who presented with their children for the first time in the hospital during the COVID 19 pandemic. A pretested, semi-structured, interviewer-administered questionnaire which was designed by the researchers was used for data collection.ResultsMinority (44.7%) of the mothers perceived masking in children as an appropriate measure for the prevention of COVID-19. The frequent reasons given by majority (55.3%) of the mothers for the inappropriateness of face mask in children included perceived difficulty in breathing (38.5%) and the child's readiness to pull it off (29.3%). A significantly higher proportion of the children whose mothers were 35 years and above, 64.2% would wear face masks when compared with 31.7% of those whose mothers were < 30 years of age (χ2 = 28.632, pConclusionMaternal perception of masking in children as an appropriate strategy for preventing COVID-19 is adjudged low in this study. Right perception is significantly enhanced by maternal educational status, employment and marital status.

The ability to generate microscale patterns and control microswimmers may be useful for engineering smart materials. Here Arlt et al. use genetically modified bacteria with fast response to changes in light intensity to produce light-induced patterns.

Hybrid models to detect dementia based on Machine Learning can provide accurate diagnoses in individuals with neurological disorders and cognitive complications caused by Human Immunodeficiency Virus (HIV) infection. This study proposes a hybrid approach, using Machine Learning algorithms associated with the multicriteria method of Verbal Decision Analysis (VDA). Dementia, which affects many HIV-infected individuals, refers to neurodevelopmental and mental disorders. Some manuals standardize the information used in the correct detection of neurological disorders with cognitive complications. Among the most common manuals used are the DSM-5 (Diagnostic and Statistical Manual of Mental Disorders, 5th edition) of the American Psychiatric Association and the International Classification of Diseases, 10th edition (ICD-10)—both published by World Health Organization (WHO). The model is designed to explore the predictive of specific data. Furthermore, a well-defined database data set improves and optimizes the diagnostic models sought in the research.

Gelareh Eslamian, Caroline Wilson, Robin J Young Academic Unit of Clinical Oncology, Weston Park Hospital, Sheffield, UK Abstract: Eribulin is a novel microtubule-targeting agent that is approved for the treatment of patients with locally advanced or metastatic breast cancer who have previously received treatment with an anthracycline and a taxane in either the adjuvant or metastatic setting. Eribulin induces mitotic catastrophe leading to cell death but has other important antitumor effects, including reversal of epithelial–mesenchymal transition and remodeling of the tumor vasculature. Eribulin was licensed for the treatment of advanced breast cancer based on results from two large randomized Phase III clinical trials. Current clinical trials of eribulin for breast cancer are evaluating response to treatment earlier in the patient pathway and in combination with other therapeutic agents. This review provides a short overview of emerging new data on the mode of action of eribulin in breast cancer. Keywords: eribulin, microtubule-targeting agents, breast cancer

Recent advances in microscopy, computing power and image processing have enabled the analysis of ever larger datasets of movies of microorganisms to study their behaviour. However, techniques for analysing the dynamics of individual cells from such datasets are not yet widely available in the public domain. We recently demonstrated significant phenotypic heterogeneity in the adhesion of Escherichia coli bacteria to glass surfaces using a new method for the high-throughput analysis of video microscopy data. Here, we present an in-depth analysis of this method and its limitations, and make public our algorithms for following the positions and orientations of individual rod-shaped bacteria from time-series of 2D images to reconstruct their trajectories and characterise their dynamics. We demonstrate in detail how to use these algorithms to identify different types of adhesive dynamics within a clonal population of bacteria sedimenting onto a surface. The effects of measurement errors in cell positions and of limited trajectory durations on our results are discussed.

We report a high-throughput technique for characterising the motility of spermatozoa using differential dynamic microscopy. A movie with large field of view (∼10mm2) records thousands of cells (e.g. ≈ 5000 cells even at a low cell density of 20 × 106 cells/ml) at once and yields averaged measurements of the mean ([Formula: see text]) and standard deviation (σ) of the swimming speed, head oscillation amplitude (A0) and frequency (f0), and the fraction of motile spermatozoa (α). Interestingly, we found that the measurement of α is facilitated because the swimming spermatozoa enhance the motion of the non-swimming population. We demonstrate the ease and rapidity of our method by performing on-farm characterisation of bull spermatozoa motility, and validate the technique by comparing laboratory measurements with tracking. Our results confirm the long-standing theoretical prediction that [Formula: see text] for swimming spermatozoa.

Fibroblast growth factor 8 (FGF8) is a potent morphogen that regulates the ontogenesis of gonadotropin-releasing hormone (GnRH) neurons, which control the hypothalamus-pituitary-gonadal (HPG) axis, and therefore reproductive success. Indeed, FGF8 and FGFR1 deficiency severely compromises vertebrate reproduction in mice and humans and is associated with Kallmann Syndrome (KS), a congenital disease characterized by hypogonadotropic hypogonadism associated with anosmia. Our laboratory demonstrated that FGF8 signaling through FGFR1, both of which are KS-related genes, is necessary for proper GnRH neuron development in mice and humans. Here, we investigated the possibility that non-genetic factors, such as the epigenome, may contribute to KS onset. For this purpose, we developed an embryonic explant model, utilizing the mouse olfactory placode (OP), the birthplace of GnRH neurons. We show that TET1, which converts 5-methylcytosine residues (5mC) to 5-hydroxymethylated cytosines (5hmC), controls transcription of Fgf8 during GnRH neuron ontogenesis. Through MeDIP and ChIP RT-qPCR we found that TET1 bound to specific CpG islands on the Fgf8 promoter. We found that the temporal expression of Fgf8 correlates with not only TET1 binding, but also with 5hmC enrichment. siRNA knockdown of Tet1 reduced Fgf8 and Fgfr1 mRNA expression. During this time period, Fgf8 also switched histone status, most likely via recruitment of EZH2, a major component of the polycomb repressor complex-2 (PRC2) at E13.5. Together, these studies underscore the significance of epigenetics and chromatin modifications to temporally regulated genes involved in KS.

Introduction: Perioperative delirium in elderly hip fracture patients has been correlated with significant morbidity. The purpose of this study was to determine the preoperative risk factors for and short-term sequelae of postoperative delirium in geriatric hip fracture patients. Methods: We queried the American College of Surgeons National Surgical Quality Improvement Program to identify geriatric (≥65 years) patients who sustained operative hip fractures in 2016. Cohorts of patients with and without documented postoperative delirium were identified. Primary data on patient demographics and comorbidities were collected and correlated with postoperative complications and hip fracture outcome measures. Multivariate regression was used to compute risk-adjusted odds ratios (OR) of risk factors and sequelae of delirium. Results: In total, 8,439 geriatric hip fracture patients were identified of whom 2,569 patients (30.4%) had postoperative delirium. Age (OR 1.03 [1.02-1.04, p < 0.001), white race (OR 1.54 [1.19-2.00], p = 0.001), American Society of Anesthesiologists classification (OR 1.20 [1.07-1.36], p = 0.003), baseline dementia (OR 2.46 [2.11-2.86], p < 0.001), and preoperative delirium (OR 10.06 [8.12-12.45], p < 0.001) were independent risk factors for postoperative delirium in multivariate analysis. Patients with postoperative delirium had a significantly higher risk-adjusted 30-day mortality (12.0% vs. 4.8%, OR 2.22 [1.74-2.84], p < 0.001) and morbidity profile. Postoperative delirium was also independently associated with higher rates of discharge to (OR 1.65 [1.32-2.06], p < 0.001) and prolonged stay in (OR 1.79 [1.53-2.09], p < 0.001) an inpatient facility, hospital readmission (OR 1.94 [1.58-2.38], p < 0.001) and hospital length of stay (7.6 ± 5.0 vs. 6.1 ± 4.1 days, p < 0.001), as well as lower rates of immediate postoperative weight bearing (OR 0.73 [0.63-0.86], p < 0.001). Discussion: Postoperative delirium is a common occurrence in geriatric hip fractures with multiple risk factors. Delirium portends higher mortality and worse perioperative hospital-based outcomes. Conclusions: Multidisciplinary foreknowledge and management efforts are warranted to mitigate the risk of developing delirium, which strongly predicts perioperative morbidity, mortality, and hip fracture outcomes.

Favorable relaxation processes, high-field spectral properties, and biological compatibility have made spin-7/2 Gd3+-based spin labels an increasingly popular choice for protein structure studies using high-field electron paramagnetic resonance. However, high-field relaxation and decoherence in ensembles of half-integer high-spin systems, such as Gd3+, remain poorly understood. We report spin-lattice (T1) and phase memory (TM) relaxation times at 8.6 T (240 GHz), and we present the first comprehensive model of high-field, high-spin decoherence accounting for both the electron spin concentration and temperature. The model includes four principal mechanisms driving decoherence: energy-conserving electron spin flip-flops, direct "T1" spin-lattice relaxation-driven electron spin flip processes, indirect T1-driven flips of nearby electron spins, and nuclear spin flip-flops. Mechanistic insight into decoherence can inform the design of experiments making use of Gd3+ as spin probes or relaxivity agents and can be used to measure local average interspin distances as long as 17 nm.

Quinazolinones have pharmacological effects on vascular reactivity through different mechanisms. We synthesized 4-phenylquinazolin-2(1H)-one derivatives under microwave irradiation and tested them on the rat thoracic aorta. The prepared compounds 2a−2f were obtained in about 1 h with suitable yields (31−92%). All derivatives produced vasorelaxant effects with IC50 values ranging from 3.41 ± 0.65 µM to 39.72 ± 6.77 µM. Compounds 2c, 2e and 2f demonstrated the highest potency in endothelium-intact aorta rings (IC50 4.31 ± 0.90 µM, 4.94 ± 1.21 µM and 3.41 ± 0.65 µM respectively), and they achieved around 90% relaxation (30 μM). In aorta rings without an endothelium, the effect of compound 2f was abolished. Using the MTT assay to test for cell viability, only compound 2b induced cytotoxicity at the maximum concentration employed (30 µM). The results show that vasorelaxation by 4-phenylquinazolin-2(1H)-one derivatives might depend on the activation of a signalling pathway triggered by endothelium-derived factors.

Most bacteria swim in liquid environments by rotating one or several flagella. The long external filament of the flagellum is connected to a membrane-embedded basal body by a flexible universal joint, the hook, which allows the transmission of motor torque to the filament. The length of the hook is controlled on a nanometer scale by a sophisticated molecular ruler mechanism. However, why its length is stringently controlled has remained elusive. We engineered and studied a diverse set of hook-length variants of Salmonella enterica. Measurements of plate-assay motility, single-cell swimming speed, and directional persistence in quasi-2D and population-averaged swimming speed and body angular velocity in 3D revealed that the motility performance is optimal around the wild-type hook length. We conclude that too-short hooks may be too stiff to function as a junction and too-long hooks may buckle and create instability in the flagellar bundle. Accordingly, peritrichously flagellated bacteria move most efficiently as the distance travelled per body rotation is maximal and body wobbling is minimized. Thus, our results suggest that the molecular ruler mechanism evolved to control flagellar hook growth to the optimal length consistent with efficient bundle formation. The hook-length control mechanism is therefore a prime example of how bacteria evolved elegant but robust mechanisms to maximize their fitness under specific environmental constraints.

The integrated stress response (ISR) is activated by diverse forms of cellular stress, including endoplasmic reticulum (ER) stress, and is associated with diseases. However, the molecular mechanism(s) whereby the ISR impacts on differentiation is incompletely understood. Here, we exploited a mouse model of Metaphyseal Chondrodysplasia type Schmid (MCDS) to provide insight into the impact of the ISR on cell fate. We show the protein kinase RNA-like ER kinase (PERK) pathway that mediates preferential synthesis of ATF4 and CHOP, dominates in causing dysplasia by reverting chondrocyte differentiation via ATF4-directed transactivation of Sox9. Chondrocyte survival is enabled, cell autonomously, by CHOP and dual CHOP-ATF4 transactivation of Fgf21. Treatment of mutant mice with a chemical inhibitor of PERK signaling prevents the differentiation defects and ameliorates chondrodysplasia. By preventing aberrant differentiation, titrated inhibition of the ISR emerges as a rationale therapeutic strategy for stress-induced skeletal disorders.

Referral-level medicine is important in the veterinary curriculum, however veterinary students also need a solid base knowledge of clinically relevant, routine surgical and diagnostic skills to be clinically prepared after graduation. Exposure to a referral-only, or primarily referral caseload, does not always provide veterinary students with the routine hands-on experiences and competencies expected by the American Veterinary Medical Association Council on Education, the Royal College of Veterinary Surgeons, the Australian Veterinary Boards Council, or prospective employers. The aim of this descriptive study was to assess how a shelter medicine program can fill the companion animal caseload gap and create the necessary hands-on experiences considered essential in the veterinary curriculum. Pedagogical frameworks, course curriculum and design, student experiences, and student assessments were described for three core curricular areas (surgery, medical days, population medicine) of the Shelter Medicine Program at Mississippi State University. The shelter surgery experience provided a high-quality, high-volume spay/neuter environment where fourth-year students averaged 65 sterilization surgeries in two weeks and demonstrated a quantifiable decrease in surgical time. The shelter surgery experience added on average 9,000 small animal cases per year to the overall hospital caseload. Shelter medical days, where students provide veterinary care during on-site shelter visits, created opportunities for third-year students to directly interact with shelter animals by performing physical examinations and diagnostic testing, and to gain experience in developing treatment protocols and recommendations for commonly encountered problems. The shelter medical days experience averaged over 700 small animal cases per year and over 1,500 diagnostic procedures. Finally, students participated in 15 onsite shelter consultations where they obtained a working knowledge of biosecurity at a population level, including how to minimize the risk of infectious diseases spreading to healthy populations. Despite several challenges, results from this curricular program assessment support the aim that animal shelters and humane organizations offer opportunities that can be mutually beneficial for both animal organizations and veterinary students. The primary care caseload for the teaching institution was positively impacted, and students were better prepared to meet potential employers’ expectations and fulfill required core competencies in veterinary medical education.

Case series summary A queen, tom and four 1-year-old female offspring presented for routine neuter. Two of the littermates (cats 1 and 2) were diagnosed with a uterine abnormality during surgery. The left uterine horn of both cats appeared as a thin, solid, cord-like structure, whereas the right uterine horn of both cats appeared to have intermittent bulges consistent with pregnancy. The two other littermates, queen and tom were reproductively normal. The uteruses of the affected cats were nearly identical with a gross and histopathologic diagnosis of uterus unicornis with concurrent pregnancy. Ovaries were present, bilaterally. An oviduct was present only on the single normally developed and pregnant uterine horn in both cats. At a postoperative follow-up evaluation, abdominal ultrasound was performed on the two cats with uterine abnormalities. Cat 1 was ultrasonographically within normal limits. Cat 2 was diagnosed with ipsilateral renal agenesis on the same side as the absent uterine horn. Relevance and novel information The complexity of uterus unicornis and renal aplasia is demonstrated by this unique presentation of five related cats for ovariohysterectomy. This report raises questions regarding the genetic, environmental, hormonal or other underlying causes of this anatomic abnormality in cats that may spur additional research. This is the first publication describing uterus unicornis in gravid feline littermates, with one of the cats having ipsilateral renal agenesis. This is also the first publication to describe oviduct agenesis on the affected uterine horn in feline uterus unicornis.

ABSTRACT Piper aduncum found naturally in the Amazon and southeastern Brazil, is known for its secondary metabolites that have activity on insects. Anticarsia gemmatalis and Spodoptera frugiperda are among the major insect pests associated with agricultural production. This research evaluated the biological activity of hexane, ethyl acetate, and ethanol extracts of P. aduncum leaves on mortality and duration of larval and pupal periods, as well as weight, width, and length of A. gemmatalis and S. frugiperda pupae. The mortality of A. gemmatalis larvae in trials with P. aduncum extracts were 93.3% (hexane) and 90% (ethyl acetate), estimating LC50 of 6.35 and 5.79 mg/mL, respectively. Mortality in S. frugiperda submitted to the hexane extract ranged from 3.33% to 96.66% (LC50 of 8.22 mg/mL). The ethanol extract induced low mortality (3.33% to 23.33%). The P. aduncum extracts did not affect the development of S. frugiperda pupae. In A. gemmatalis differences in weight and length occurred. The chemical characterization was by GC-MS, which revealed that the major constituent in the hexane extract of P. aduncum was apiol (90.7%). P. aduncum extracts are important and promising components to manage A. gemmatalis and S. frugiperda, which cause extensive production losses.